Measurement of glomerular filtration rate in anesthetized and conscious rhesus monkeys (Macaca mulatta)

Carlos A. RabitoDepartment of Radiology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114

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Susan van TongerenToxicology Department, Boehringer Ingelheim, 900 Ridgebury Rd, Ridgefield, CT 06877

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Paul A. ZavorskasCharles River Laboratories, 334 South St, Shrewsbury, MA 01545

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Alain Stricker-KrongradCharles River Laboratories, 334 South St, Shrewsbury, MA 01545

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John RobbAppropriate Technology Company, 18 Graf Rd, Ste 18, Newburyport, MA 01950

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Garner T. Haupert JrMedical Services, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114

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Abstract

Objective—To validate a method to assess glomerular filtration rate (GFR) in conscious monkeys via transcutaneous radiation detection after IV injection of technetium Tc 99m pentatate(99mTc-DTPA).

Animals—4 healthy rhesus monkeys.

Procedures—On day 1, each monkey was anesthetized, lothalamate sodium I 125 (125l-iothalamate) was administered via continuous rate infusion (0.0037 MBq/min); blood and urine samples were obtained for determination of 125l-iothalamate plasma clearance variables and estimation of GFR. One dose of 99mTc-DTPA (74 MBq/kg, IV) was also administered during the 125l-iothalamate plasma clearance test, and transcutaneous measurements of technetium 99m-emitted radiation were obtained by use of an ambulatory renal monitor (ARM) applied to a brachium of each monkey. Determination of GFR by use of the ARM was repeated on days 8 and 45 in the same monkeys without anesthesia.

Results—Sensitivity, accuracy, and precision of the 2 methods were similar. By use of the ARM, GFR determined by use of the renal rate constant (κGFR) was calculated; the value obtained on day 1 under anesthesia was similar to values determined via 125l-iothalamate plasma clearance testing on the same day, but was 16% to 23% less than that measured on days 8 and 45 in conscious monkeys.

Conclusions and Clinical Relevance—The ARM method for assessment of GFR was less invasive, faster, and more convenient than the standard clearance method, but yielded comparable results. The need to train animals and size restrictions of the device may limit the use of this technique in other nonhuman animals.

Abstract

Objective—To validate a method to assess glomerular filtration rate (GFR) in conscious monkeys via transcutaneous radiation detection after IV injection of technetium Tc 99m pentatate(99mTc-DTPA).

Animals—4 healthy rhesus monkeys.

Procedures—On day 1, each monkey was anesthetized, lothalamate sodium I 125 (125l-iothalamate) was administered via continuous rate infusion (0.0037 MBq/min); blood and urine samples were obtained for determination of 125l-iothalamate plasma clearance variables and estimation of GFR. One dose of 99mTc-DTPA (74 MBq/kg, IV) was also administered during the 125l-iothalamate plasma clearance test, and transcutaneous measurements of technetium 99m-emitted radiation were obtained by use of an ambulatory renal monitor (ARM) applied to a brachium of each monkey. Determination of GFR by use of the ARM was repeated on days 8 and 45 in the same monkeys without anesthesia.

Results—Sensitivity, accuracy, and precision of the 2 methods were similar. By use of the ARM, GFR determined by use of the renal rate constant (κGFR) was calculated; the value obtained on day 1 under anesthesia was similar to values determined via 125l-iothalamate plasma clearance testing on the same day, but was 16% to 23% less than that measured on days 8 and 45 in conscious monkeys.

Conclusions and Clinical Relevance—The ARM method for assessment of GFR was less invasive, faster, and more convenient than the standard clearance method, but yielded comparable results. The need to train animals and size restrictions of the device may limit the use of this technique in other nonhuman animals.

Contributor Notes

Drs. Zavorskas and Stricker-Krongrad's present address is Charles River Laboratories, 251 Ballardvale St, Wilmington, MA.

Dr. Rabito holds interest in Cuyo Tech Incorporated. Drs. Rabito and Haupert receive consulting fees from Boehringer Ingelheim. Dr. Robb holds interest in Appropriate Technology Company.

Address correspondence to Dr. Rabito (Crabito@partners.org).
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